Photodynamic therapy (PDT) is being used experimentally to treat a wide variety of malignant tumors and certain other diseases, such as psoriasis and papillomatosis. This technology is disclosed in U.S. Pat. Nos. 4,649,151; 4,866,168; 4,889,129 and 4,932,934, the disclosures of which are incorporated herein by reference.
The PDT method utilizes a photosensitizer which accumulates in tumors and can be activated by an appropriate light source, generally a laser. In general, the treatment is limited by the need to deliver light internally, for example, by fiber optics through endoscopes. Further, depth of penetration is limited by the optical properties of the tumor tissue and is generally in the 2-5 mm range. While fiber optics can be inserted directly into tumors to deliver the light to bulky tumors, this is often not possible for technical reasons, such as tumor location and size.
U.S. Pat. No. 4,801,459 describes the release of drugs from liposomes using RF or microwaves to break the liposome. However, this patent says nothing about causing local reaction of two or more components to generate excited states or light to "activate" a material already in the tissue, such as a photosensitizer.
U.S. Pat. No. 4,891,043 requires a laser to "break" a liposome to deliver drugs or dyes to a site.
The following U.S. Pat. Nos. show the encapsulation of selected compounds in liposomes: 4,935,407; 5,004,565 and 5,006,473.
It has been established for many years that certain biological processes generate light, for example, firefly luminescence via reaction of luciferase with luciferin. Also, it is well known that certain chemical reactions generate light via excited intermediate species, for example, thermal decomposition of 1,2-dioxetanes and oxidation of malonic acid. Further, in some cases, the excited states can be trapped, causing excitation of the trapping agent. Complete descriptions of numerous such reactions can be found in Chemi- and Bioluminescence, edited by John G. Burr, Marcel Dekker Inc., New York, 1985, the disclosure of which is incorporated herein by reference. However, these types of reactions cannot be used with all photosensitizers since some photosensitizers accumulate in normal tissues as well as in tumors.
It is a purpose of the invention to allow photodynamic therapy to be carried out without the necessity of using expensive and difficult to maintain laser systems.
It is another purpose of the invention to allow photodynamic therapy to treat distant metastases, that is, tumors in difficult to reach locations or where the exact location of the tumor is unknown.
It is a further purpose of the invention to allow photodynamic therapy to treat larger tumor masses.